A Pilot Study of Tranilast for Cardiomyopathy of Muscular Dystrophy.

Abstract

Objective Heart failure is currently the most serious complication of muscular dystrophy. The transient receptor potential cation channel, subfamily V, member 2 (TRPV2) is a stretch-sensitive Ca channel. In damaged myocytes or cardiomyocytes, TRPV2 translocates to the cytoplasmic membrane and enhances Ca influx, triggering cell damage. Evidence suggests that the inhibition of TRPV2 may be a new therapeutic target in heart failure. We found that tranilast, which is widely used as an anti-allergic drug, inhibits TRPV2. A pilot study was conducted to assess the safety and efficacy of tranilast in muscular dystrophy patients with cardiomyopathy. Methods After obtaining informed consent, two muscular dystrophy patients with advanced heart failure took tranilast (300 mg/day) for three months. Blood tests, echocardiography, electrocardiography (ECG), Holter ECG, analyses of the TRPV2 expression in peripheral mononuclear cells, and circulating micro ribonucleic acid profiling were performed to assess the safety and efficacy of tranilast. Results The brain natriuretic peptide levels decreased after treatment. The expression of TRPV2 on the cytoplasmic membrane of peripheral mononuclear cells was enhanced before treatment and was decreased after treatment. Some heart-related micro ribonucleic acids (miR-208a-5p, miR-223-3p) were elevated and then decreased after treatment. Some adverse events, including the potentiation of warfarin, the worsening of renal dysfunction, an increased heart rate and premature ventricular contractions, were observed. Conclusion Tranilast can inhibit TRPV2 and can be effective for treating heart failure, even in patients with muscular dystrophy. Although careful attention is needed, the inhibition of TRPV2 can be a new treatment target for cardiomyopathy. A multi-center trial is planned.

• Authors: Tsuyoshi Matsumura, Misa Matsui, Yuko Iwata, Masanori Asakura, Toshio Saito, Harutoshi Fujimura, Saburo Sakoda
• Journal: Internal medicine (Tokyo, Japan) (Intern Med) Vol. 57 Issue 3 Pg. 311-318 (Feb 01 2018) ISSN: 1349-7235 [Electronic] Japan
• PMID: 29093384 (Publication Type: Case Reports, Journal Article)

Chemical References

• Calcium Channel Blockers
• ortho-Aminobenzoates
• tranilast

Topics

• Calcium Channel Blockers (therapeutic use)
• Drug Administration Schedule
• Heart Failure (diagnosis, drug therapy, etiology)
• Humans
• Male
• Middle Aged
• Muscular Dystrophies (complications)
• Pilot Projects
• ortho-Aminobenzoates (therapeutic use)